Effects of ethanol on GABA(A) receptors in GABAergic and glutamatergic presynaptic nerve terminals.

Masahito Wakita, Min-Chul Shin, Satomi Iwata, Kiku Nonaka, Norio Akaike

Research Division for Life Sciences, Kumamoto Health Science University, 325 Izumimachi, Kumamoto, 861-5598, Japan.

The Journal of pharmacology and experimental therapeutics 2012 Jun

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Ethanol (EtOH) has a number of behavioral effects, including intoxication, amnesia, and/or sedation, that are thought to relate to the activation of GABA(A) receptors. However, GABA(A) receptors at different cellular locations have different sensitivities to EtOH. The present study used the "synaptic bouton" preparation where we could stimulate nerve endings on mechanically dissociated single rat hippocampal CA1 and CA3 pyramidal neurons and investigate the effects of EtOH on presynaptic and postsynaptic GABA(A) receptors. Low concentrations of EtOH (10 mM) had no effect on postsynaptic GABA(A) and glutamate receptors or voltage-dependent Na(+) and Ca(2+) channels. Higher concentrations (≥100 mM) could significantly inhibit these current responses. EtOH at 10 mM had no direct effect on inhibitory postsynaptic currents (IPSCs) and excitatory postsynaptic currents (EPSCs) evoked by focal stimulation of single boutons [evoked IPSCs (eIPSCs) and evoked EPSCs (eEPSCs)]. However, coapplication of 10 mM EtOH with muscimol decreased the amplitude of eIPSCs and eEPSCs and increased their paired-pulse ratio. The effects on eEPSCs were reversed by bicuculline. Coapplication of muscimol and EtOH significantly increased the frequency of spontaneous IPSCs and EPSCs. The EtOH effects on the postsynaptic responses and eEPSCs were similar in neurons from neonatal and mature rats. These results revealed that low concentrations of EtOH can potentiate the activation of presynaptic GABA(A) receptors to inhibit evoked GABA and glutamate release. These results indicate a high sensitivity of presynaptic GABA(A) receptor to EtOH, which needs to be accounted for when considering the cellular mechanisms of EtOH's physiological responses.

Citation

Masahito Wakita, Min-Chul Shin, Satomi Iwata, Kiku Nonaka, Norio Akaike. Effects of ethanol on GABA(A) receptors in GABAergic and glutamatergic presynaptic nerve terminals. The Journal of pharmacology and experimental therapeutics. 2012 Jun;341(3):809-19